title: Hyperglycemia following recovery from hypoglycemia worsens endothelial damage and thrombosis activation in type 1 diabetes and in healthy controls.
abstract: OBJECTIVE
  Hypoglycemia produces thrombosis activation, but little attention has been paid to the effects of hyperglycemia following recovery from hypoglycemia on thrombosis activation.
  
  
  RESULTS
  In both twenty-two healthy subjects and twenty-one matched persons with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normo-glycemia or hyperglycemia for another 2 h. After this, normal glycemia was maintained for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. In both controls and people with diabetes, the recovery with normo-glycemia was accompanied by a significant improvement of Von Willebrand factor (vWF), prothrombin fragment 1 + 2 (F1 + 2), thrombin-antithrombin III-complexes (TAT), P-selectin, plasminogen activator inhibitor-1 (PAI-1), nitrotyrosine and 8-iso-prostaglandin F2α (8-iso-PGF2α) (p < 0.01 vs hypoglycemia for all the parameters), all directly affected by hypoglycemia itself (p < 0.01 vs baseline for all the parameters). On the contrary, the recovery with hyperglycemia after hypoglycemia worsens all these parameters (p < 0.01 vs normoglycemia for all the parameters), an effect persisting even after the additional 6 h of normo-glycemia. The effect of hyperglycemia following hypoglycemia was partially counterbalanced when vitamin C was infused (p < 0.01 vs hyperglycemia alone for all the parameters), suggesting that hyperglycemia following hypoglycemia may activate thrombosis through the oxidative stress production.
  
  
  CONCLUSIONS
  This study shows that, in type 1 diabetes as well as in controls, the way in which recovery from hypoglycemia takes place could play an important role in favoring the activation of thrombosis and oxidative stress, widely recognized cardiovascular risk factors.
authors.affiliation: Department of Endocrinology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain. Electronic address: aceriell@clinic.ub.es.
authors.forename: A
authors.initials: A
authors.lastname: Ceriello
authors.affiliation: Department of Endocrinology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain.
authors.forename: A
authors.initials: A
authors.lastname: Novials
authors.affiliation: Department of Endocrinology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ortega
authors.affiliation: Department of Endocrinology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain; Metabolic and Nutrition Research Center on Diabetes, Italian National Research Center on Aging, INRCA-IRCCS, Ancona, Italy; Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica, Sesto San Giovanni (MI), Italy.
authors.forename: G
authors.initials: G
authors.lastname: Pujadas
authors.affiliation: Department of Endocrinology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: La Sala
authors.affiliation: Department of Endocrinology, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM), Spain; Metabolic and Nutrition Research Center on Diabetes, Italian National Research Center on Aging, INRCA-IRCCS, Ancona, Italy; Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica, Sesto San Giovanni (MI), Italy.
authors.forename: R
authors.initials: R
authors.lastname: Testa
authors.affiliation: Metabolic and Nutrition Research Center on Diabetes, Italian National Research Center on Aging, INRCA-IRCCS, Ancona, Italy.
authors.forename: A R
authors.initials: AR
authors.lastname: Bonfigli
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, IRCCS Gruppo Multimedica, Sesto San Giovanni (MI), Italy.
authors.forename: S
authors.initials: S
authors.lastname: Genovese
mesh_terms: D000328:Adult; D000990:Antithrombin III / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000209:etiology; D007003:Hypoglycemia / Q000150:complications / Q000628:therapy*; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D019007:P-Selectin / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D013927:Thrombosis / Q000209:etiology / Q000473:pathology*; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D019007:P-Selectin; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D011498:Protein Precursors; C051321:SERPINE1 protein, human; C046193:antithrombin III-protease complex; D014841:von Willebrand Factor; C075750:8-epi-prostaglandin F2alpha; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D000990:Antithrombin III; D011516:Prothrombin; D015237:Dinoprost; D010447:Peptide Hydrolases; D001205:Ascorbic Acid
keywords: Hyperglycemia; Hypoglycemia; Oxidative stress; Thrombosis